Gene Therapy with Modified Autologous Hematopoietic Stem Cells for Patients with Mucopolysaccharidosis Type II

Inclusion Criteria:

1. Written informed consent from a legally authorized guardian.

2. Male, age at consent ≥3 months and ≤22 months.

3. Normal cognitive function or mild cognitive dysfunction (patient has a DevelopmentQuotient (DQ) score ≥70 at screening as determined by the Bayley Scale of InfantDevelopment-third edition (BSID-III), cognitive domain), or assessed as normal oronly mildly impaired by experienced neuropsychologist.

4. Close male relative with known severe (progressive neuronopathic) phenotype ofMPSII, or genotype associated with progressive neuronopathic phenotype. This is tobe confirmed by the independent expert reviewers.

5. IDS activity ≤10% of the Lower Limit of Normal as measured in leucocytes or plasma,plus either (1) a normal enzyme activity level of at least one other sulfatase (torule out multiple sulfatase deficiency) as measured in leucocytes, or (2) adocumented mutation in the IDS gene.

6. Medically stable and able to accommodate the protocol requirements, including travelwithout placing an undue burden on the patient/patient's family, as determined bythe CI.

7. Patients and their parents/legal guardians must be willing and able to comply withstudy restrictions and to commit to attend clinic for the required duration duringthe study and follow-up period as specified in the protocol.

Exclusion Criteria:

1. The patient has previously received stem cell or gene therapy

2. The patient has received modified intravenous ERT or intra-thecal ERT in a trialsetting.

3. Patient currently enrolled in another interventional clinical trial

4. The patient has a history of poorly controlled seizures

5. Hemizygous for mutation known to be associated with non-neuropathic phenotype

6. The patient is currently receiving psychotropic or other medications which, in theCI's opinion, would be likely to substantially confound test results

7. The patient has received any investigational medicinal product (including Genistein)within 30 days prior to the Baseline visit or is scheduled to receive anyinvestigational medicinal product during the course of the study

8. Documented Human Immunodeficiency Virus (HIV) infection (positive HIV RNA and/oranti-p24 antibodies)

9. Malignant neoplasia (except local skin cancer) or a documented history of hereditarycancer syndrome. Patients with a prior successfully treated malignancy and asufficient follow-up to exclude recurrence (based on oncologist opinion) can beincluded after discussion and approval by the Medical Monitor

10. Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndromeand acute myeloid leukaemia, or other serious haematological disorders

11. The patient has a medical condition or extenuating circumstance that, in the opinionof the CI, might compromise the patient's ability to comply with protocolrequirements, the patient's well-being or safety, or the interpretability of thepatient's clinical data

12. Visual or hearing impairment sufficient to preclude adequate neurodevelopmentaltesting

13. Severe behavioural disturbances due to reasons other than MPS II and likely tointerfere with protocol compliance, as determined by the CI

14. Known sensitivity to Busulfan

15. The receipt of live vaccinations within 30 days prior to treatment start

16. Known sensitivity to DMSO